Individuals with medical implants are often at risk of developing life-threatening thrombi on the surface of these devices. Fibrinogen (Fgn) facilitates platelet recruitment by laterally aggregating at its αC domains into interconnected fibers that provide structure for thrombi. Thus, one method of preventing thrombogenesis is by inhibiting this process. The calculated optimal adsorption cites of the in silico human Fgn NJm on a hydrophobic thermoplastic surface model were congruent with existing literature, suggesting that on a polystyrene (PS) surface, Fgn is positioned with its αC domain exposed. Allowing a molecule to bind to the exposed αC domain will prevent the Fgn proteins from laterally aggregating. This study generated an in vitro bovine model of fiber formation on a hydrophobic PS surface to investigate the proficiency of a hydrophilic 14-peptide sequence derived from the Aα635-648 region of fibronectin, P-12 (PSHISKYILRWRPK), in achieving that end. Various amounts of bovine Fgn and P-12 were plated on PS and submerged in phosphate-buffered saline at various intervals. 100 μg/mL of Fgn acted as the monolayer that would initiate fibrin cluster formation, an additional 4 mg/mL of Fgn that, uninterrupted, would aggregate to form fibers, and 10μM of P-12 were added to investigate its impact on Fgn polymerization. Large fibers were observed in the absence of P-12, supporting the previous reports that the αC domains of the monolayer were opened by the hydrophobic interaction. Significantly smaller fibers were present when the P-12 was added alongside the surface monolayer, suggesting P-12 displaced certain sections, while minimal fiber formation occurred when P-12 was added afterward, which suggests that P-12 binds with Fgn to prevent the formation of fibrin clusters. This experiment confirms that P-12 blocks the ability of Fgn to execute fiber formation and that P-12 can displace Fgn from surfaces. If medical implants are manufactured with hydrophobic surfaces, this study suggests the introduction of P-12 can be used to mitigate thrombosis.

Development of a short peptide to prevent non-thrombogenic clot formation on hydrophobic surfaces

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